Project 6 will focus on the most basic neurobiological effects of DBS, i.e. how does long-lasting, high- frequency electrical stimulation of subcortical white matter affect the axons, synapses, and neurons of prefrontal regions of neocortex? To this end, we will use contemporary methods of in vitro cellular neurophysiology to make high resolution measurements from groups of specific, genetically identified cortical neurons and their synaptic connections. Several lines of GFP-expressing mice will be used. Experiments will focus on the influence of DBS on conduction properties of afferent and efferent axons, and identified types of excitatory and inhibitory synaptic connections and their local cortical circuits. We will also use a c- fos-GFP mouse line to ask how high frequency stimulation in vivo alters the physiological properties of c-fos- expressing neurons. The results of this project should illuminate the basic mechanisms of DBS in brain structures relevant to OCD. RELEVANCE (See instmctions): Obsessive Compulsive Disorder (OCD) is a chronic psychiatric illness that affects 2-3% of the worldwide population. This is disease is in the top ten dehabilitating diseases. This study will examine the neural network and mechanisms that underiie behaviors associated with OCD. These behaviors not limited to OCD, but are associated with a range of affective and addictive disorders. The collective proposed studies will generate new hypotheses of how dysfunctions within these brain networks are expressed across diseases and provide insight into the mechanisms underlying normal behavioral responses. PROJECT/